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AMES - A special set of sugars found on some disease-causing
pathogens helps those pathogens fight the body's natural
defenses as well as vaccines, say two Iowa State University
researchers.

This discovery may be a first step in understanding a disease
family that includes tuberculosis for which there are currently
no good vaccines or cures.

Nicola Pohl, professor of chemistry, and Christine Petersen,
assistant professor of veterinary pathology, discovered that a
natural coating of sugar interacts with the body's defense
cells to dampen its own immune response.

The findings are published in the current online issue of the
Journal of the American Chemical Society.

Pohl and Petersen began studying persistent pathogens such as
tuberculosis and the parasite Leishmania five years ago when
they noticed that some types of the parasite can make people
sick, while others do not.

"One of the things I was curious about was that pathogenic
strains of Leishmania have a different sugar coating on them
than nonpathogenic strains," Pohl said.

"We asked the question 'Is it possible that just the
sugar coating is enough to make something pathogenic or
nonpathogenic?'" she said.

Leishmania-associated diseases are not usually found in the
United States, but have been observed in soldiers returning
from the Middle East. The diseases can cause unsightly sores,
and can last a period of months, according to Pohl.

The diseases are often fatal to dogs in the United States.

"The problem is, in places like Bangladesh, where people
are in a nutritionally compromised state, peoples' immune
systems aren't strong enough, and the disease can be
fatal," said Pohl.

Normally, when a disease-causing agent enters the body, cells
called macrophages engulf and start to destroy the agent.

Leishmania-type diseases are resistant to this process.

To test the theory on the resistance effect of the sugar
coating, Pohl and Petersen developed an experiment that
required creating small beads measuring one micron in diameter
to mimic the pathogens.

One group of beads was then coated with a type of sugar that is
similar to that of Leishmania. Another set of beads was coated
with a lactose-type sugar that isn't harmful to the cell. A
third had no coating.

The beads were then introduced into macrophages.

When the uncoated beads were introduced into the macrophages,
the cells noticed the beads and started an immune response, as
they should.

When the lactose-covered beads were introduced, they were also
recognized and removed.

When the Leishmania-sugar covered beads were introduced, the
macrophages took a much longer time to recognize their
presence. Then, the immune defense system slowed down or
dampened the attacks.

This dampening, Petersen and Pohl showed, is due to an
interaction between the sugar on the bead and Toll-like
receptor2 (TLR2) within the macrophage.

"There is something inherent about the sugars themselves,
and the difference in these sugars, that dampens your normal
response to the pathogen," said Pohl.

Pohl said they don't yet know exactly what that interaction
is or how it works, but she hopes that this research may lead
to more research eventually beating the disease.

"Right now we don't have good therapeutics against
Leishmaniasis, and we don't have a vaccine for it, so
basically you can't do anything about it," she added.

"The more information we have about this, the more we
learn about how to circumvent this to get an effective
vaccine," she said.

Petersen credits the partnership with Pohl as one of the key
factors in understanding the problem.

Pohl's chemistry background doesn't often lead her to
look at whole organisms and Petersen, as a veterinary
pathologist, previously didn't look at the chemistry.

"Many of these critical sub-molecular interactions are
often glossed over by immunologists and biologists," said
Petersen. "But the work Nikki and I just published shows
that they can make a much larger difference in how a pathogen
is sensed by the immune system."

The research staff also included Alex Osanya, an assistant
scientist in veterinary pathology and Eun-Ho Song, a former
graduate student in chemistry.

Contacts

Quick Look

Two Iowa State University researchers discovered that a special
set of sugars found on some disease-causing pathogens helps
those pathogens fight the body's natural defenses as well
as vaccines. This discovery may be a first step in
understanding a disease family that includes tuberculosis for
which there are currently no good vaccines or cures.

Quote

We asked the question 'Is it possible that just the sugar
coating is enough to make something pathogenic or
nonpathogenic?'

Nicola Pohl
Professor of Chemistry

Quote

Many of these critical sub-molecular interactions are often
glossed over by immunologists and biologists. But the work
Nikki and I just published shows that they can make a much
larger difference in how a pathogen is sensed by the immune
system.